The epidermal growth factor receptor (EGFR or ErbB) family of receptor tyrosine kinases includes ErbB1 (known also as epidermal growth factor receptor (EGFR)), ErbB2 (known also as human epidermal growth factor receptor 2 (HER2)), ErbB3 (known also as HER3), and ErbB4 (known also as HER4). The receptor tyrosine kinases of the ErbB family may form a homodimer or heterodimer by combination with a ligand and may activate the signal transduction pathway of mitogen-activated protein kinase kinase (MAP2K, MEK, or MAPKK)/mitogen-activated protein kinase (MAPK), or the signal transduction pathway of phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB or Akt). The ErbB family of proteins is reported to be related to the occurrence, progress, or prognosis of cancer.
Erbitux® (Cetuximab) or Tarceva® (Erlotinib) as ErbB1 inhibitors and Herceptin® (Trastuzumab) or Tyverb® (Lapatinib) as ErbB2 inhibitors, are commercially available anti-cancer drugs. However, a large number of patients are unresponsive to these anti-cancer drugs, and these anti-cancer drugs are accompanied with development of resistance. A specific inhibitor antibody to ErbB3 or ErbB4 has not yet been made commercially available.
Therefore, there is a need for the development of new anti-cancer drugs that may cope with the genetic diversity of cancer and overcome resistance to anti-cancer drugs.